Tourette syndrome is a complex neurological disorder that usually becomes evident between 4 and 18 years of age. The disorder is characterized by chronic motor and phonic tics, often with a variety of behavioural comorbidities; in particular, attention-deficit hyperactivity disorder, obsessive–compulsive disorder, and impulse control disorder. The cause of Tourette syndrome is poorly understood. Although environmental factors are proposed to have a role, genetic factors are thought to be the primary contributors to the pathogenesis of this disorder. However, identification of the causative gene mutations or risk alleles has proved to be difficult. Early studies on the genetics of Tourette syndrome focused on multigenerational lineages and suggested Mendelian inheritance, but subsequent segregation analyses point to a more-complex inheritance pattern. A monogenic inheritance model has been proposed following the identification of rare genetic mutations associated with the Tourette syndrome phenotype. Although no specific mutations have found to directly cause Tourette syndrome, genetic findings may enable identification of the affected pathways, and could lead to the development of new treatment strategies. In this Review, we provide an overview of the genetics of Tourette syndrome and highlight how this knowledge has improved our understanding of the possible pathogenic mechanisms of this neurological disorder.
Tourette syndrome is a complex neurological disorder characterized by chronic motor and phonic tics, often accompanied by a variety of behavioural comorbidities
Genetics seem to have the most critical role in the aetiopathogenesis of Tourette syndrome, but the disorder may occur as the result of complex interactions between environmental and genetic factors
Cytogenetic and linkage analyses have uncovered a number of loci and several genetic mutations that are associated with Tourette syndrome
Discoveries of genetic mutations associated with the Tourette syndrome phenotype support the conclusion that the disorder has an autosomal dominant inheritance pattern
The genetic variants associated with Tourette syndrome may have important cumulative effects and could contribute to the phenotypic variability observed in patients with this disorder
Genetic findings have led to a better understanding of the possible pathogenic mechanisms of Tourette syndrome, which may guide the development of new treatment strategies
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Jankovic, J. & Kurlan, R. Tourette syndrome: evolving concepts. Mov. Disord. 26, 1149–1156 (2011).
Kurlan, R. Clinical practice. Tourette's syndrome. N. Engl. J. Med. 363, 2332–2338 (2010).
Jankovic, J. Tourette's syndrome. N. Engl. J. Med. 345, 1184–1192 (2001).
Cheung, M. Y., Shahed, J. & Jankovic, J. Malignant Tourette syndrome. Mov. Disord. 22, 1743–1750 (2007).
Jankovic, J., Gelineau-Kattner, R. & Davidson, A. Tourette's syndrome in adults. Mov. Disord. 25, 2171–2175 (2010).
Robertson, M. M. The prevalence and epidemiology of Gilles de la Tourette syndrome. Part 1: the epidemiological and prevalence studies. J. Psychosom. Res. 65, 461–472 (2008).
Centers for Disease Control and Prevention (CDC). Prevalence of diagnosed Tourette syndrome in persons aged 6–17 years—United States (2007). MMWR Morb. Mortal. Wkly Rep. 58, 581–585 (2009).
State, M. W. The genetics of Tourette disorder. Curr. Opin. Genet. Dev. 21, 302–309 (2011).
Jankovic, J. Treatment of hyperkinetic movement disorders. Lancet Neurol. 8, 844–856 (2009).
Robertson, M. M. Tourette syndrome, associated conditions and the complexities of treatment. Brain 123, 425–462 (2000).
Olson, S. Making sense of Tourette's. Science 305, 1390–1392 (2004).
Paschou, P. et al. Indications of linkage and association of Gilles de la Tourette syndrome in two independent family samples: 17q25 is a putative susceptibility region. Am. J. Hum. Genet. 75, 545–560 (2004).
Khalifa, N. & von Knorring, A. L. Tourette syndrome and other tic disorders in a total population of children: clinical assessment and background. Acta Paediatr. 94, 1608–1614 (2005).
Pauls, D. L., Raymond, C. L., Stevenson, J. M. & Leckman, J. F. A family study of Gilles de la Tourette syndrome. Am. J. Hum. Genet. 48, 154–163 (1991).
Pauls, D. L., Cohen, D. J., Heimbuch, R., Detlor, J. & Kidd, K. K. Familial pattern and transmission of Gilles de la Tourette syndrome and multiple tics. Arch. Gen. Psychiatry 38, 1091–1093 (1981).
Parraga, H. C., Parraga, M. I., Spinner, L. R., Kelly, D. P. & Morgan, S. L. Clinical differences between subjects with familial and non-familial Tourette's syndrome: a case series. Int. J. Psychiatry Med. 28, 341–351 (1998).
Hyde, T. M., Aaronson, B. A., Randolph, C., Rickler, K. C. & Weinberger, D. R. Relationship of birth weight to the phenotypic expression of Gilles de la Tourette's syndrome in monozygotic twins. Neurology 42, 652–658 (1992).
Price, R. A., Kidd, K. K., Cohen, D. J., Pauls, D. L. & Leckman, J. F. A twin study of Tourette syndrome. Arch. Gen. Psychiatry 42, 815–820 (1985).
Grados, M. A., Mathews, C. A. & Tourette Syndrome Association International Consortium for Genetics. Latent class analysis of Gilles de la Tourette syndrome using comorbidities: clinical and genetic implications. Biol. Psychiatry 64, 219–225 (2008).
Voelker, R. Scientists use neuroimaging, genetic studies to probe biology of Tourette syndrome. JAMA 292, 909–911 (2004).
Baron, M., Shapiro, E., Shapiro, A. & Rainer, J. D. Genetic analysis of Tourette syndrome suggesting major gene effect. Am. J. Hum. Genet. 33, 767–775 (1981).
Curtis, D., Robertson, M. M. & Gurling, H. M. Autosomal dominant gene transmission in a large kindred with Gilles de la Tourette syndrome. Br. J. Psychiatry 160, 845–849 (1992).
Pauls, D. L. & Leckman, J. F. The inheritance of Gilles de la Tourette's syndrome and associated behaviors. Evidence for autosomal dominant transmission. N. Engl. J. Med. 315, 993–997 (1986).
State, M. W. The genetics of child psychiatric disorders: focus on autism and Tourette syndrome. Neuron 68, 254–269 (2010).
Kurlan, R., Eapen, V., Stern, J., McDermott, M. P. & Robertson, M. M. Bilineal transmission in Tourette's syndrome families. Neurology 44, 2336–2342 (1994).
Walkup, J. T. et al. Family study and segregation analysis of Tourette syndrome: evidence for a mixed model of inheritance. Am. J. Hum. Genet. 59, 684–693 (1996).
Ercan-Sencicek, A. G. et al. L-histidine decarboxylase and Tourette's syndrome. N. Engl. J. Med. 362, 1901–1908 (2010).
Singer, H. S. Tourette's syndrome: from behaviour to biology. Lancet Neurol. 4, 149–159 (2005).
Hanna, P. A., Janjua, F. N., Contant, C. F. & Jankovic, J. Bilineal transmission in Tourette syndrome. Neurology 53, 813–818 (1999).
Lichter, D. G., Dmochowski, J., Jackson, L. A. & Trinidad, K. S. Influence of family history on clinical expression of Tourette's syndrome. Neurology 52, 308–316 (1999).
McMahon, W. M. et al. Bilineal transmission and phenotypic variation of Tourette's disorder in a large pedigree. J. Am. Acad. Child. Adolesc. Psychiatry 35, 672–680 (1996).
Singer, H. S. Tourette syndrome and other tic disorders. Handb. Clin. Neurol. 100, 641–657 (2011).
Petek, E. et al. Disruption of a novel gene (IMMP2L) by a breakpoint in 7q31 associated with Tourette syndrome. Am. J. Hum. Genet. 68, 848–858 (2001).
Verkerk, A. J. et al. CNTNAP2 is disrupted in a family with Gilles de la Tourette syndrome and obsessive compulsive disorder. Genomics 82, 1–9 (2003).
Abelson, J. F. et al. Sequence variants in SLITRK1 are associated with Tourette's syndrome. Science 310, 317–320 (2005).
Lawson-Yuen, A., Saldivar, J. S., Sommer, S. & Picker, J. Familial deletion within NLGN4 associated with autism and Tourette syndrome. Eur. J. Hum. Genet. 16, 614–618 (2008).
Poliak, S. et al. Caspr2, a new member of the neurexin superfamily, is localized at the juxtaparanodes of myelinated axons and associates with K+ channels. Neuron 24, 1037–1047 (1999).
Proenca, C. C., Gao, K. P., Shmelkov, S. V., Rafii, S. & Lee, F. S. Slitrks as emerging candidate genes involved in neuropsychiatric disorders. Trends Neurosci. 34, 143–153 (2011).
Bruses, J. L. Identification of gene transcripts expressed by postsynaptic neurons during synapse formation encoding cell surface proteins with presumptive synaptogenic activity. Synapse 64, 47–60 (2010).
Jamain, S. et al. Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism. Nat. Genet. 34, 27–29 (2003).
Furuta, K., Ichikawa, A., Nakayama, K. & Tanaka, S. Membrane orientation of the precursor 74-kDa form of L-histidine decarboxylase. Inflamm. Res. 55, 185–191 (2006).
O'Rourke, J. A., Scharf, J. M., Yu, D. & Pauls, D. L. The genetics of Tourette syndrome: a review. J. Psychosom. Res. 67, 533–545 (2009).
Ezugha, H. et al. Microarray analysis in children with developmental disorder or epilepsy. Pediatr. Neurol. 43, 391–394 (2010).
Ringman, J. M. & Jankovic, J. Occurrence of tics in Asperger's syndrome and autistic disorder. J. Child. Neurol. 15, 394–400 (2000).
Boghosian-Sell, L., Comings, D. E. & Overhauser, J. Tourette syndrome in a pedigree with a 7;18 translocation: identification of a YAC spanning the translocation breakpoint at 18q22.3. Am. J. Hum. Genet. 59, 999–1005 (1996).
Kroisel, P. M. et al. Candidate region for Gilles de la Tourette syndrome at 7q31. Am. J. Med. Genet. 101, 259–261 (2001).
Burri, L. et al. Mature DIABLO/Smac is produced by the IMP protease complex on the mitochondrial inner membrane. Mol. Biol. Cell 16, 2926–2933 (2005).
Petek, E. et al. Molecular and genomic studies of IMMP2L and mutation screening in autism and Tourette syndrome. Mol. Genet. Genomics 277, 71–81 (2007).
Patel, C. et al. Translocation breakpoint at 7q31 associated with tics: further evidence for IMMP2L as a candidate gene for Tourette syndrome. Eur. J. Hum. Genet. 19, 634–639 (2011).
Lu, B. et al. A mutation in the inner mitochondrial membrane peptidase 2-like gene (Immp2l) affects mitochondrial function and impairs fertility in mice. Biol. Reprod. 78, 601–610 (2008).
Ma, Y., Mehta, S. L., Lu, B. & Li, P. A. Deficiency in the inner mitochondrial membrane peptidase 2-like (Immp21) gene increases ischemic brain damage and impairs mitochondrial function. Neurobiol. Dis. 44, 270–276 (2011).
Leonard, J. V. & Schapira, A. H. Mitochondrial respiratory chain disorders II: neurodegenerative disorders and nuclear gene defects. Lancet 355, 389–394 (2000).
Whatley, S. A., Curti, D. & Marchbanks, R. M. Mitochondrial involvement in schizophrenia and other functional psychoses. Neurochem. Res. 21, 995–1004 (1996).
Belloso, J. M. et al. Disruption of the CNTNAP2 gene in a t(7;15) translocation family without symptoms of Gilles de la Tourette syndrome. Eur. J. Hum. Genet. 15, 711–713 (2007).
Poot, M. et al. Disruption of CNTNAP2 and additional structural genome changes in a boy with speech delay and autism spectrum disorder. Neurogenetics 11, 81–89 (2010).
Chou, I. C., Wan, L., Liu, S. C., Tsai, C. H. & Tsai, F. J. Association of the Slit and Trk-like 1 gene in Taiwanese patients with Tourette syndrome. Pediatr. Neurol. 37, 404–406 (2007).
Deng, H., Le, W. D., Xie, W. J. & Jankovic, J. Examination of the SLITRK1 gene in Caucasian patients with Tourette syndrome. Acta Neurol. Scand. 114, 400–402 (2006).
Fabbrini, G. et al. A large Italian family with Gilles de la Tourette syndrome: clinical study and analysis of the SLITRK1 gene. Mov. Disord. 22, 2229–2234 (2007).
Orth, M. et al. Autosomal dominant myoclonus-dystonia and Tourette syndrome in a family without linkage to the SGCE gene. Mov. Disord. 22, 2090–2096 (2007).
Pasquini, M. et al. Psychopathological features of obsessive–compulsive disorder in an Italian family with Gilles de la Tourette syndrome not linked to the SLITRK1 gene. Psychiatry Res. 161, 109–111 (2008).
Verkerk, A. J. et al. Genetic and clinical analysis of a large Dutch Gilles de la Tourette family. Mol. Psychiatry 11, 954–964 (2006).
Zimprich, A. et al. Sequence analysis of the complete SLITRK1 gene in Austrian patients with Tourette's disorder. Psychiatr. Genet. 18, 308–309 (2008).
Keen-Kim, D. et al. Overrepresentation of rare variants in a specific ethnic group may confuse interpretation of association analyses. Hum. Mol. Genet. 15, 3324–3328 (2006).
Scharf, J. M. et al. Lack of association between SLITRK1 var321 and Tourette syndrome in a large family-based sample. Neurology 70, 1495–1496 (2008).
Wendland, J. R., Kruse, M. R. & Murphy, D. L. Functional SLITRK1 var321, varCDfs and SLC6A4 G56A variants and susceptibility to obsessive–compulsive disorder. Mol. Psychiatry 11, 802–804 (2006).
Miranda, D. M. et al. Association of SLITRK1 to Gilles de la Tourette syndrome. Am. J. Med. Genet. B Neuropsychiatr. Genet. 150B, 483–486 (2009).
O'Roak, B. J. et al. Additional support for the association of SLITRK1 var321 and Tourette syndrome. Mol. Psychiatry 15, 447–450 (2010).
Aruga, J. & Mikoshiba, K. Identification and characterization of Slitrk, a novel neuronal transmembrane protein family controlling neurite outgrowth. Mol. Cell Neurosci. 24, 117–129 (2003).
Kajiwara, Y., Buxbaum, J. D. & Grice, D. E. SLITRK1 binds 14-3-3 and regulates neurite outgrowth in a phosphorylation-dependent manner. Biol. Psychiatry 66, 918–925 (2009).
Stillman, A. A. et al. Developmentally regulated and evolutionarily conserved expression of SLITRK1 in brain circuits implicated in Tourette syndrome. J. Comp. Neurol. 513, 21–37 (2009).
Katayama, K. et al. Slitrk1-deficient mice display elevated anxiety-like behavior and noradrenergic abnormalities. Mol. Psychiatry 15, 177–184 (2010).
Devor, E. J. & Magee, H. J. Multiple childhood behavioral disorders (Tourette syndrome, multiple tics, ADD and OCD) presenting in a family with a balanced chromosome translocation (t1;8)(q21.1;q22.1). Psychiatr. Genet. 9, 149–151 (1999).
Matsumoto, N. et al. Breakpoint sequences of an 1;8 translocation in a family with Gilles de la Tourette syndrome. Eur. J. Hum. Genet. 8, 875–883 (2000).
Crawford, F. C. et al. Translocation breakpoint in two unrelated Tourette syndrome cases, within a region previously linked to the disorder. Hum. Genet. 113, 154–161 (2003).
Singh, D. N., Howe, G. L., Jordan, H. W. & Hara, S. Tourette's syndrome in a black woman with associated triple X and 9p mosaicism. J. Natl Med. Assoc. 74, 675–682 (1982).
Taylor, L. D. et al. 9p monosomy in a patient with Gilles de la Tourette's syndrome. Neurology 41, 1513–1515 (1991).
Jankovic, J. & Deng, H. Candidate locus for chorea and tic disorders at 15q? Pediatr. Neurol. 37, 70–73 (2007).
Kerbeshian, J., Severud, R., Burd, L. & Larson, L. Peek-a-boo fragile site at 16d associated with Tourette syndrome, bipolar disorder, autistic disorder, and mental retardation. Am. J. Med. Genet. 96, 69–73 (2000).
Shelley, B. P., Robertson, M. M. & Turk, J. An individual with Gilles de la Tourette syndrome and Smith–Magenis microdeletion syndrome: is chromosome 17p11.2 a candidate region for Tourette syndrome putative susceptibility genes? J. Intellect. Disabil. Res. 51, 620–624 (2007).
Dehning, S., Riedel, M. & Muller, N. Father-to-son transmission of 6;17 translocation in Tourette's syndrome. Am. J. Psychiatry 165, 1051–1052 (2008).
Robertson, M. M., Shelley, B. P., Dalwai, S., Brewer, C. & Critchley, H. D. A patient with both Gilles de la Tourette's syndrome and chromosome 22q11 deletion syndrome: clue to the genetics of Gilles de la Tourette's syndrome? J. Psychosom. Res. 61, 365–368 (2006).
Clarke, R. A., Fang, Z. M., Diwan, A. D. & Gilbert, D. L. Tourette syndrome and Klippel–Feil anomaly in a child with chromosome 22q11 duplication. Case Report Med. http://dx.doi.org/10.1155/2009/361518.
Donnai, D. Gene location in Tourette syndrome. Lancet 1, 627 (1987).
Cuker, A., State, M. W., King, R. A., Davis, N. & Ward, D. C. Candidate locus for Gilles de la Tourette syndrome/obsessive compulsive disorder/chronic tic disorder at 18q22. Am. J. Med. Genet. A 130A, 37–39 (2004).
State, M. W. et al. Epigenetic abnormalities associated with a chromosome 18(q21–q22) inversion and a Gilles de la Tourette syndrome phenotype. Proc. Natl Acad. Sci. USA 100, 4684–4689 (2003).
Brett, P. M., Curtis, D., Robertson, M. M. & Gurling, H. M. Neuroreceptor subunit genes and the genetic susceptibility to Gilles de la Tourette syndrome. Biol. Psychiatry 42, 941–947 (1997).
Kubota, Y. et al. Increased methamphetamine-induced locomotor activity and behavioral sensitization in histamine-deficient mice. J. Neurochem. 83, 837–845 (2002).
Haas, H. L., Sergeeva, O. A. & Selbach, O. Histamine in the nervous system. Physiol. Rev. 88, 1183–1241 (2008).
Bloch, M., State, M. & Pittenger, C. Recent advances in Tourette syndrome. Curr. Opin. Neurol. 24, 119–125 (2011).
Lei, J. et al. Mutation screening of the HDC gene in Chinese Han patients with Tourette syndrome. Am. J. Med. Genet. B Neuropsychiatr. Genet. 159B, 72–76 (2012).
Brioni, J. D., Esbenshade, T. A., Garrison, T. R., Bitner, S. R. & Cowart, M. D. Discovery of histamine H3 antagonists for the treatment of cognitive disorders and Alzheimer's disease. J. Pharmacol. Exp. Ther. 336, 38–46 (2011).
Knight, S. et al. Linkage analysis of Tourette syndrome in a large Utah pedigree. Am. J. Med. Genet. B Neuropsychiatr. Genet. 153B, 656–662 (2010).
Curtis, D. et al. Genome scan of Tourette syndrome in a single large pedigree shows some support for linkage to regions of chromosomes 5, 10 and 13. Psychiatr. Genet. 14, 83–87 (2004).
Laurin, N., Wigg, K. G., Feng, Y., Sandor, P. & Barr, C. L. Chromosome 5 and Gilles de la Tourette syndrome: Linkage in a large pedigree and association study of six candidates in the region. Am. J. Med. Genet. B Neuropsychiatr. Genet. 150B, 95–103 (2009).
Simonic, I., Gericke, G. S., Ott, J. & Weber, J. L. Identification of genetic markers associated with Gilles de la Tourette syndrome in an Afrikaner population. Am. J. Hum. Genet. 63, 839–846 (1998).
Simonic, I. et al. Further evidence for linkage of Gilles de la Tourette syndrome (GTS) susceptibility loci on chromosomes 2p11, 8q22 and 11q23–24 in South African Afrikaners. Am. J. Med. Genet. 105, 163–167 (2001).
Barr, C. L. et al. Genome scan for linkage to Gilles de la Tourette syndrome. Am. J. Med. Genet. 88, 437–445 (1999).
The Tourette Syndrome Association for Genetics. A complete genome screen in sib pairs affected by Gilles de la Tourette syndrome. Am. J. Hum. Genet. 65, 1428–1436 (1999).
Zhang, H. et al. Genomewide scan of hoarding in sib pairs in which both sibs have Gilles de la Tourette syndrome. Am. J. Hum. Genet. 70, 896–904 (2002).
Feng, R., Leckman, J. F. & Zhang, H. Linkage analysis of ordinal traits for pedigree data. Proc. Natl Acad. Sci. USA 101, 16739–16744 (2004).
The Tourette Syndrome Association for Genetics. Genome scan for Tourette disorder in affected-sibling-pair and multigenerational families. Am. J. Hum. Genet. 80, 265–272 (2007).
Horn, S. Gilles de la Tourette syndrome. Clin. Neuropharmacol. 24, 125–128 (2001).
Comings, D. E. Clinical and molecular genetics of ADHD and Tourette syndrome. Two related polygenic disorders. Ann. NY Acad. Sci. 931, 50–83 (2001).
Cerullo, J., Reimschisel. T. & Singer, H. in Genetic and neurobiological basis for Tourette syndrome. Treating Tourette Syndrome and Tic Disorders: A Guide for Practitioners (eds Woods, D. W. et al.) 58–84 (Guilford Press, New York, 2007).
Leckman, J. F. Tourette's syndrome. Lancet 360, 1577–1586 (2002).
Talebizadeh, Z. et al. Novel splice isoforms for NLGN3 and NLGN4 with possible implications in autism. J. Med. Genet. 43, e21 (2006).
Blasi, F. et al. Absence of coding mutations in the X-linked genes neuroligin 3 and neuroligin 4 in individuals with autism from the IMGSAC collection. Am. J. Med. Genet. B Neuropsychiatr. Genet. 141B, 220–221 (2006).
Zhang, C. et al. A neuroligin-4 missense mutation associated with autism impairs neuroligin-4 folding and endoplasmic reticulum export. J. Neurosci. 29, 10843–10854 (2009).
Riviere, J. B. et al. Association of intronic variants of the BTBD9 gene with Tourette syndrome. Arch. Neurol. 66, 1267–1272 (2009).
Dehning, S. et al. A genetic variant of HTR2C may play a role in the manifestation of Tourette syndrome. Psychiatr. Genet. 20, 35–38 (2010).
Bevilacqua, L. et al. A population-specific HTR2B stop codon predisposes to severe impulsivity. Nature 468, 1061–1066 (2010).
Crane, J. et al. Family-based genetic association study of DLGAP3 in Tourette syndrome. Am. J. Med. Genet. B Neuropsychiatr. Genet. 156B, 108–114 (2011).
Sundaram, S. K. et al. Exome sequencing of a pedigree with Tourette syndrome or chronic tic disorder. Ann. Neurol. 69, 901–904 (2011).
Jankovic, J. & Mejia, N. I. Tics associated with other disorders. Adv. Neurol. 99, 61–68 (2006).
Romstad, A. et al. Dopa-responsive dystonia and Tourette syndrome in a large Danish family. Arch. Neurol. 60, 618–622 (2003).
Yaltho, T. C., Jankovic, J. & Lotze, T. The association of Tourette syndrome and dopa-responsive dystonia. Mov. Disord. 26, 359–360 (2011).
Orstavik, R. E., Tommerup, N., Eiklid, K. & Orstavik, K. H. Non-random X chromosome inactivation in an affected twin in a monozygotic twin pair discordant for Wiedemann-Beckwith syndrome. Am. J. Med. Genet. 56, 210–214 (1995).
Sykiotis, G. P. et al. Oligogenic basis of isolated gonadotropin-releasing hormone deficiency. Proc. Natl Acad. Sci. USA 107, 15140–15144 (2010).
Diaz-Anzaldua, A. et al. Tourette syndrome and dopaminergic genes: a family-based association study in the French Canadian founder population. Mol. Psychiatry 9, 272–277 (2004).
Toft, M., Mata, I. F., Kachergus, J. M., Ross, O. A. & Farrer, M. J. LRRK2 mutations and Parkinsonism. Lancet 365, 1229–1230 (2005).
Lesch, K. P. et al. Genome-wide copy number variation analysis in attention-deficit/hyperactivity disorder: association with neuropeptide Y gene dosage in an extended pedigree. Mol. Psychiatry 16, 491–503 (2011).
Sebat, J. et al. Strong association of de novo copy number mutations with autism. Science 316, 445–449 (2007).
Sundaram, S. K., Huq, A. M., Wilson, B. J. & Chugani, H. T. Tourette syndrome is associated with recurrent exonic copy number variants. Neurology 74, 1583–1590 (2010).
Grados, M. A. The genetics of obsessive–compulsive disorder and Tourette syndrome: an epidemiological and pathway-based approach for gene discovery. J. Am. Acad. Child. Adolesc. Psychiatry 49, 810–819 (2010).
So, H. C., Li, M. & Sham, P. C. Uncovering the total heritability explained by all true susceptibility variants in a genome-wide association study. Genet. Epidemiol. 35, 447–456 (2011).
Deng, H., Gu, S., Jankovic, J. LINGO1 variants in essential tremor and Parkinson's disease. Acta Neurol. Scand. 125, 1–7 (2012).
Merette, C. et al. Significant linkage for Tourette syndrome in a large French Canadian family. Am. J. Hum. Genet. 67, 1008–1013 (2000).
Breedveld, G. J., Fabbrini, G., Oostra, B. A., Berardelli, A. & Bonifati, V. Tourette disorder spectrum maps to chromosome 14q31.1 in an Italian kindred. Neurogenetics 11, 417–423 (2010).
Hao Deng was supported by National Natural Science Foundation of China (30871351), Sheng Hua Scholars Program and Outstanding Youth Foundation of Central South University, China, the Fundamental Research Funds for the Central Universities (2011JQ014), Program for New Century Excellent Talents in University of Ministry of Education of P. R. China (NCET-080563), Research Fund for the Doctoral Program of Higher Education of China (20110162110026) and Grant for the Foster Key Subject of the Third Xiangya Hospital (Clinical Laboratory Diagnostics). Kai Gao was supported by Mittal Students Innovative Projects of Central South University, China (11MX28). Joseph Jankovic was supported by the Diana Helis Henry Medical Research Foundation, the National Parkinson Foundation and Huntington Disease Society of America, Baylor College of Medicine Center of Excellence.
The authors declare no competing financial interests.
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Deng, H., Gao, K. & Jankovic, J. The genetics of Tourette syndrome. Nat Rev Neurol 8, 203–213 (2012). https://doi.org/10.1038/nrneurol.2012.26
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